Human storage disease cells in culture and a mutant GM1 gangliosidosis cat have been used for these studies. Study of physiologic and biochemical parameters of these models is aimed at defining the milieu in which enzyme replacement studies are conducted. Macrophages derived from circulating monocytes will survive in culture for approximately two weeks. Under special conditions, dividing cultures have been established without the use of transforming virus. These cells have survived more than six months. Alterations of lysosomal enzymatic activities have been recorded in both short and long term cultures. Estimation of lectin occurrence and function in these cells has been evaluated. The ability of cells to incorporate added lipids has been measured. Catabolism of added lipid has been compared in control and disease cells. Studies in the cat mutant have revealed that human placental Beta-galactosidase can be delivered to brain following blood-brain barrier opening. The placental enzyme loses about half its activity in human plasma and thus may not be ideal for enzyme replacement trials. Preparation of a more stable enzyme from feline or bovine tissues has begun. Further characterization of the cat model as a model for enzyme replacement in neurological disorders is progressing.